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Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand.

ABSTRACT: When exposed to nutrient excess and insulin resistance, pancreatic β-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming β-cell plasticity in later life is a poorly studied area. The imprinted Igf2 (insulin-like growth factor 2) gene is highly transcribed during early life and has been identified in recent genome-wide association studies as a type 2 diabetes susceptibility gene in humans. Hence, here we investigate the long-term phenotypic metabolic consequences of conditional Igf2 deletion in pancreatic β-cells (Igf2^βKO) in mice. We show that autocrine actions of IGF2 are not critical for β-cell development, or for the early post-natal wave of β-cell remodelling. Additionally, adult Igf2^βKO mice maintain glucose homeostasis when fed a chow diet. However, pregnant Igf2^βKO females become hyperglycemic and hyperinsulinemic, and their conceptuses exhibit hyperinsulinemia and placentomegalia. Insulin resistance induced by congenital leptin deficiency also renders Igf2^βKO females more hyperglycaemic compared to leptin-deficient controls. Upon high-fat diet feeding, Igf2^βKO females are less susceptible to develop insulin resistance. Based on these findings, we conclude that in female mice, autocrine actions of β-cell IGF2 during early development determine their adaptive capacity in adult life.

SUBMITTER: Sandovici I

PROVIDER: S-EPMC8032793 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Integrin and autocrine IGF2 pathways control fasting insulin secretion in β-cells.

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Fetus-derived IGF2 matches placental development to fetal demand

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-01 | GSE125434 | GEO

Fetus-derived IGF2 matches placental development to fetal demand [microarray]

Project description:We used microarrays to identify genes that are transcriptionally dysregulated between Igf2EpiKO mutants and littermates controls at E19

2020-07-01 | GSE125278 | GEO

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Fetus-derived IGF2 matches placental development to fetal demand [RNA-seq]

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Fetus-derived IGF2 matches placental development to fetal demand II [RNA-seq]

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